Diagnostic tests frequently are performed on biological samples, such as whole blood or urine that include substantial amounts of particulate matter that can clog microchannels of an assay device and interfere with reaction and detection systems. To avoid the problem of particulate in clinical samples, they are typically centrifuged or filtered before sample analysis.
Particulate removal by filtration in the prior art has largely focused on forced transverse flow mechanisms. To achieve removal of particulates, incorporation of a filter into an assay device has been described in the prior art. For example, U.S. Pat. No. 4,477,575, to Vogel, et al. “Process and Composition for Separating Plasma or Serum from Whole Blood” uses a transverse flow of blood through stacked filter elements filter to separate red blood cells from plasma. However, sealing of the filter in the device to achieve effective filtration, and not allow sample to bypass the filter, is a problem with this technology. The products are bulky in thickness. A small capillary or gap between the filter and the filter chamber walls can allow peripheral non-filtering flows. Particulate matter which travels around the filter decreases the filtration efficiency, repeatability, and may cause the filter to be unacceptable for certain applications. Techniques, such as using glues, tapes and the like have been used to seal a filter into the filter chamber of such devices. The use of these materials to affect sealing has produced variable, and often poor sealing. Additionally, these sealing methods can result in absorption of variable amounts of the sealing compound into the filter.
Another drawback of prior art filter devices is the short transverse fluid flow path through a filter's depth. Transverse flow paths in a conventionally shaped filter (a filter with a length, width and substantially thinner depth) is the distance between the top and the bottom of the filter, the filter depth commonly referred to as the filter thickness. Filters are generally 0.1 mm to 6 mm thick, this short flow path can provide poor separation efficiency.
An alternate filter configuration would be to provide a filter with a long lateral flow path, such as is described in “Devices for Incorporating Filters for Filtering Fluid Samples”, U.S. Pat. No. 6,391,265, to Buechler, et al. Buechler applies sample fluid to one end of a planar filter and collects filtrate at the other end of the same filter. However, this single filter technology has the disadvantage that the same filter dealing with the gross particulate of the sample also has to handle the final fine filtration.
In view of the above, a need exists for a specialized filtration system that can remove bulk particulates from fluids in a thin package without clogging or peripheral flows. It would be desirable to have a filter that addresses both large bulk particulates and fine particulates in a long flow path without the need for pressurized flows. The present invention provides these and other features that will be apparent upon review of the following.